α-Actinin-4, which displays 87% sequence identity to α-actinin-1 [9], is detected at points of cell-cell contact [12] and interacts with focal adhesion constituents, including vinculin and the cytoplasmic domain of β integrins [3], [6], [10].
To identify such interactions, cell membrane extracts were used in Far-western blots and HAMLET was shown to bind α-actinins; major F-actin cross-linking proteins and focal adhesion constituents.
We used different thresholds to study the groups produced and found at a cutting threshold of 20% a cluster of gene categories that include the terms "response to glucose stimulus", "collagen type VI", "muscle organ development", "sarcolema", "extracellular matrix structural constituent", "focal adhesion", and "PI3k-Akt signal pathway".
(B ) Focal glutamatergic stimulation of constituent neurons in a model network (n,p) = (330,0.125).
This resulted in the following 11 modules: Immune, KRAS, Proliferation1 (defined by genes common to two to four enlarged signatures), Proliferation2 (defined by genes common to five or more enlarged signatures), RNA splicing, Rb pathway, Sterol biosynthesis, Extracellular matrix constituent (ECM), Focal adhesion, Negative regulation of proliferation, and Apoptosis.
Distinct pathways are enriched: toll-like receptor signaling, focal adhesion, extracellular matrix constituents and remodeling machinery, and extracellular matrix (ECM) receptor interaction pathways.
Our experiments revealed a convergent prominent surface depletion of cholesterol along with certain proteins, of which many are constituents of focal adhesion sites, lipid rafts and caveolae (or functionally related to them), in PSEN deficient cells [ 147].
Moreover, they suggest that targeting FAK and other constituents of the focal adhesion complex, such as integrins, p130Cas, talin, or paxillin, holds the potential to inactivate specifically the oncogenic activities of TGF-β in malignant MECs.
This set of model networks also generated network-wide bursts within 200 300 ms following brief focal glutamatergic stimulation of five or more constituent neurons in agreement with focal glutamate un-caging experiments in neonatal mouse slices, which showed that simultaneous stimulation of 4 9 preBötC neurons can trigger inspiratory bursts with similar latency (Kam et al., 2013b).
ILK is an intracellular serine/threonine protein kinase that is a constituent of integrin-mediated cell-matrix focal adhesions, structures that mediate cell adhesion and signal transduction between the extracellular matrix and the intracellular compartment [ 6].
